1. Field of the Invention
The present invention is directed to a simple and inexpensive liquid or dry reagent assay system for detecting manganese in body fluids in microgram per liter concentrations. More specifically, the manganese assay of this invention is directed to the optical detection of a chromogenic reaction, such as the oxidation of a redox indicator, catalyzed by a manganese porphyrin complex. Sufficient oxygen, in a concentration near the saturation value or in the form of free access to air, must be present.
2. Discussion of the Prior Art
Manganese is known to be a cofactor in certain biochemical enzymatic systems, such as the glycosyl transferases (enzymes which are necessary for polysaccharide and glycoprotein synthesis). Manganese is also involved in cholesterol biosynthesis and therefore manganese deficiency can cause decreased serum cholesterol.
Although iron, zinc, and copper are considered essential because clinical evidence of deficiency exists, manganese is generally accepted as essential for humans on the basis of its proven role in manganese-dependent enzymes rather than on direct evidence of human deficiency. Manganese supplementation is sometimes necessary to alleviate blood clotting defects and hypocholesterolemia in manganese-deficient experimental lab animals. It has been postulated that manganese-dependent glycosyl transferase activity may be needed for synthesis of normal prothrombin, a glycoprotein.
Manganese metal enzymes incorporate manganese in the +2 or +3 valence state and include pyruvate carboxylase and superoxide dismutase. Known manganeseactivated enzymes include hydrolases, kinases, decarboxylases, and transferases.
Manganese is absorbed in the small intestine, but absorbance can be hindered by calcium, phosphorus, ferric citrate, and soy protein. Manganese deficiency can also be caused by dietary deficiency or by metal ion competitors, such as copper, iron and magnesium.
However, manganese homeostasis appears to be regulated through adjustments in body excretion rather than by intestinal absorption. The liver can typically adjust the amount of manganese in the body by altering the amount of biliary excretion. Average manganese dietary intakes generally vary from about 2.5-8.3 mg/d (milligrams per day). The estimated adequate and safe intake of manganese is about 2.5-5.0 mg/d for adults.
Chronic manganese poisoning has occurred in miners, foundry workers, welders, and workers manufacturing drugs, pottery, ceramics, glass, varnish, and food additives. The symptoms are schizophreniclike psychiatric effects and neurological disorders clinically similar to Parkinson's disease. The similarity between symptoms of manganese poisoning and Parkinson's disease has led to the discovery of a link between manganese and catecholamine metabolism. Decreases in striatal dopamine are seen in both syndromes, and administration of L-dopa (adopamine precursor) is effective in alleviating several of the common symptoms of Mn poisoning. Treatment of human manganese intoxications may also include various therapies for respiratory symptoms and the administration of metal chelators such as EDTA to reduce physiological burden.
Serum manganese levels typically increase following industrial exposure, acute hepatitis, and myocardial infarction. Suggestions have been made that manganese levels may relate to bone defects and a number of other physiological problems. As a result, determining manganese levels in body fluid provides valuable medical information and certainly will provide valuable medical information in the future when more is known of the medical significance of this ion.